Exenatide did not reduce major cardiovascular outcomes in type 2 diabetes

While exenatide can be considered a second-line option for patients with type 2 diabetes
and some may prefer its once-weekly dosing, those at high cardiovascular risk should
receive agents with demonstrated cardiovascular benefit, according to an ACP Journal
Club commentary.

GLP-1 analogues lower serum glucose by suppressing glucagon and enhancing insulin
secretion in response to hyperglycemia; exenatide is one of six GLP-1 analogues approved
for treatment of T2DM. EXSCEL is the fourth placebo-controlled trial to report CV
outcome results for GLP-1 analogues. Like lixisenatide, liraglutide, and semaglutide,
exenatide was noninferior to placebo for MACE outcomes in patients with T2DM and high
CV risk. However, whereas liraglutide and semaglutide also reduced major CV events
compared with usual care, no CV benefit was shown for lixisenatide or exenatide.

The lack of CV benefit for lixisenatide may be explained by differences in the study
population, shorter follow-up, and a smaller reduction in HbA1c levels compared with
other GLP-1 analogue trials. However, these factors were comparable between EXSCEL
and trials of liraglutide and semaglutide. Why exenatide failed to reduce CV outcomes
is unclear. One reason may be that almost half of patients (43%) discontinued the
drug prematurely, which is substantially higher than in other trials and may have
attenuated potential benefits. The efficacy of exenatide may also be lower than for
liraglutide and semaglutide. Head-to-head comparisons of GLP-1 analogues for CV outcomes
are lacking; however, liraglutide is associated with a greater reduction in HbA1c
levels and body weight than exenatide.

Exenatide can be considered a second-line option for patients with T2DM because safety
is similar to that of other GLP-1 analogues. Patients may also prefer the convenience
of once-weekly dosing. However, for T2DM patients at high CV risk, agents with demonstrated
CV benefit should be selected.

Internal medicine physicians are specialists who apply scientific knowledge and clinical expertise to the diagnosis, treatment, and compassionate care of adults across the spectrum from health to complex illness. ACP Diabetes Monthly provides a monthly summary for internists about relevant news in diabetes. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.